SURGICAL CEMENTS

Abstract: There is described a surgical cement comprising a bulking agent, a polymerisable monomer and an activator characterised in that the polymerisable monomer is an acrylate; methods for its preparation and its use.

Description: SURGICAL CEMENTS The present invention relates to cements and, in particular surgical cements such as bone cements and dental cements. Bone cements are frequently used in the fixation of prostheses to living bone. Such cements are typically polymeric materials. It is known to use acrylic monomers in the preparation of such polymeric cements, however, they suffer from the disadvantage that residual low molecular weight acrylates may be present in the cements and the cements may suffer from fatigue fractures. In addition, excessive heat may be generated on curing known cements. Improved bone cements are known from European Patent Application No.218471. Bone cements described therein comprise a solid powder phase, eg. a bulking agent, comprising n-butyl methacrylate. It is also known to use polyacrylates as, eg. film coatings in the area of woundcare, for example, British Patent No. GB 1278572 describes the use of monomers such as methoxyethyl methacrylate in the preparation of woundcare films. We have now surprisingly found that certain monomeric acrylates are useful as polymerisable monomers in the preparation of surgical cements. According to the invention we provide a surgical cement comprising a bulking agent, a polymerisable monomer and an activator characterised in that the polymerisable monomer is an acrylate. The acrylate according to the invention may be a methacrylate and especially a compound of formula I, CH, CH 3 CCO 2 (CH 2 ) n X in which n is an integer from 1 to 6, and X is halogen, alkoxy C1 to 6, or (tr ialkylsiloxy) silyl. When X is halogen it may be bromo, fluoro, iodo but preferably chloro. When X is (trialkylsiloxy)silyl, the alkyl group defined therein may be alkyl C1 to 6, preferably alkyl C1 to 4 and especially methyl. It is not essential, but preferable, that the three alkyl groups in the trialkylsiloxy moiety are the same. The integer n is preferably from 1 to 4. When X is halogen, n is preferably 1 to 3 and especially 2. When X is (trialkylsiloxy)silyl, n is preferably 2 to 4 and especially 3. Thus, the most preferred silyl methacrylate is tris (trimethylsiloxy)-3-silylpropyl methacrylate (TRIS) which is available from Fluorochem in the UK. The most preferred haloalkyl methacrylate is 2-chloroethyl methacrylate (CEMA) which is available from Lancaster Synthesis in the UK. The surgical cement according to the invention may comprise a solid and a liquid component system. The solid component may comprise a bulking agent whilst the liquid component comprises a polymerisable monomer as hereinbefore defined and an activator. The bulking agent usually comprises a powdered methacrylate polymer, eg. a methacrylate such as polymethyl methacrylate (PMMA). Alternatively, the bulking agent may contain a compound or a mixture of compounds of formula I in polymerised form. Any conventionally known activators may be used, but preferred activators are toluidines and especially N-alkyl C1 to 6 toluidines, eg. N,N -dialkyl toluidines such as N,N-dimethyl toluidine. A polymerisation initiator will be required for the cement to cure. The initiator may be included in the solid component. Such initiators include radical initiators, such as peroxides, eg. benzoyl peroxide, thus polymerisation of the monomer, leading to cement setting or curing may start spontaneously when the solid and liquid components are mixed. Alternatively, redox initiators may be used. A redox initiator may be included in the solid or liquid component. Curing can be initiated in the presence of a redox initiator by the addition of water. Preferred oxidising or reducing agents of redox catalysts are those described in European Patent No.94222. One such preferred initiator may be sodium metabisulphite/Cu (II). The solid and liquid components may be supplied as a premixed cement. Polymerisation of the premixed cement may be initiated either by the addition of a radical initiator, or alternatively a redox initiator may be included in the premixed cement such that the initiation may be commenced by the addition of water. In order to avoid premature setting it is essential that the initiator and the activator be in separate components of the system. In the case of radical activated cements the activator, is preferably in the liquid component and thus the initiator is preferably in the solid component, or alternatively the initiator may be added separately, eg. to the premixed cement. It is a particular advantage of the redox catalysed system that the initiation reaction is catalysed by the addition of water which may be added separately. The cement according to the invention may optionally comprise a radio-opaque material. Such radio-opaque materials are preferably incorporated into the solid component phase. Any conventional radio-opaque materials may be used, but preferred materials include salts, such as zirconium and/or barium salts, eg. zirconium dioxide and/or barium sulphate. By the inclusion of monomers such as compounds of formula I in either the polymerised form or as monomeric components, an improved surgical cement can be formulated which benefits from having one or more of the following properties: (i) a lower glass transition temperature material such as TRIS which has a crack blunting function and as such improves the fatigue properties of the surgical cement, (ii) reduced odour; and (iii) radio-opacity. In addition, if incorporating a compound of formula I in the polymerised form in the liquid component or a premixed cement this reduces the concentration of polymerisable double bonds prior to set and hence reduces the amount of heat generated for a specific quantity of cement. A readily activatable cement can be produced which, eg. on exposure to a water-activated polymerisation catalyst, produces a cement of good strength. The present invention in a still further aspect provides the use of a compound of formula I in the manufacture of a surgical cement or a component of a surgical cement as hereinbefore described. Generally the compound of formula I accounts for 0.5 to 50% w/w of the solid and liquid component system or of the premixed cement. The present invention is a still further aspect provides the use of a compound of formula I in the manufacture of a surgical cement or a component of a surgical cement as hereinbefore described. A water curable composition according to the invention may include those water-activatable vinyl polymerisation catalysts described in European Patent No.94222. Suitable vinyl polymerisation catalysts of this type are well known in the literature. Where the catalyst is a redox catalyst, the premixed cement may be in association with the oxidising agent or reducing agent or, preferably, both. The amount of catalyst used in the polymerisation process, eg. in association with the premixed cement, is suitably OJ to 10% by weight and preferably 0.2 approximately 3%, eg. 0.2 to 2% by weight of the prepolymer. Desirably, in surgical cements of the present invention, those components containing polymerisable material, may be in association with a polymerisation inhibitor to prevent premature polymerisation during its preparation and storage. Suitable polymerisation inhibitors include polymerisation inhibitors of the art. A favoured inhibitor for preventing premature polymerisation of such polymerisable materials, during storage is p-methoxyphenol. In use, curing of the cements may be brought about by either mixing of the solid and liquid components or adding a suitable initiator or water to the premixed cement. By the term surgical cement we mean bone cements and/or dental cements, although bone cements are preferred. According to the invention we also provide a method of fixing a prosthesis into a patient which comprises the application of a surgical cement according to the invention to an implantable prosthesis prior or during implant. By the term prosthesis we include surgical, ie. orthopaedic, or dental, ie. orthodontic prostheses. The invention will now be illustrated, but in no way limited by the following Examples. Example 1 The liquid component for a 4 bone cement formulations are shown in Table I. Formulation 1 was the control. For each formulation each of the ingredients was measured into a small beaker and mixed thoroughly. TABLE I Formulation No. 1 2 3 4 Methyl methacrylate 0ml 19ml 18ml 16ml NN dimethyl toluidine .4ml .4ml .4ml .4ml TRIS - 1ml 2ml 4ml For each of the above formulations 33.6g medium MW polymethylmethacrylate powder was mixed with 5.9g zirconium dioxide and 0.4g benzoyl peroxide. To this the required liquid component was added and stirred in for 1 minute, evacuated for 1.5 minutes and then poured into dumbell moulds. After 30 minutes curing was complete and the dumbells were removed from their moulds. The dumbells were tested for ultimate tensile strength. The results are illustrated in Table II. TABLE Formulation No. Mean Tensile Strength (M/Pa) 1 23.3 2 24.5 3 25.5 Example 2 The liquid component for 3 bone cement formulations are shown in Table I. Formulation 2 was the negative control and 3 the positive control. For each formulation each of the ingredients was measured into a small beaker and mixed thoroughly. TABLE I Formulation No. 1 2 3 Methyl methacrylate _ 20ml 20ml Chloroethyl methacrylate 20ml _ _ NN dimethyl toluidine 0.4ml 0.4ml 0.4ml TABLE II Formulation No. 1 2 3 Medium MW poly methyl 36.3g 36.3g 36.3g methacrylate Zirconium dioxide _ _ 5.9g Benzoyl peroxide 0.4g 0.4g 0.4g Each of the powder components were made up by mixing the dry ingredients in a 4oz bottle. To each the required liquid component was added and stirred in for 1 minute, evacuated for 1.5 minutes and then poured into dumbell moulds. After 30 minutes curing was complete and the dumbells were removed from their moulds. The dumbells were x-rayed to determine relative film exposures.

Claims: CLAIMS 1. A surgical cement comprising a bulking agent, a polymerisable monomer and an activator characterised in that the polymerisable monomer is an acrylate. 2. A surgical cement according to claim 1 wherein the acrylate is a methacrylate. 3. A surgical cement according to claim 2 wherein the methacrylate is a compound of formula I, CH„ I I CH 3 CCO 2 (CH 2 ) n X I in which n is an integer from 1 to 6, and X is halogen, alkoxy C1 to 6, or (trialkylsiloxy) silyl. 4. A surgical cement according to claim 3 wherein X is chloro. 5. A surgical cement according to claim 3 wherein X is (trialkylsiloxy) silyl. 6. A surgical cement according to claim 3 wherein the compound of formula I is 2-chloroethyl methacrylate. 7. A surgical cement according to claim 3 wherein the compound of formula I is tris(trimethylsiloxy)-3-siiylpropyl methacrylate. 8. A surgical cement according to any one of the previous claims comprising a solid and a liquid component system. 9. A surgical cement according to claim 8 wherein the solid component comprises a bulking agent. 10. A surgical cement according to claim 8 wherein the bulking agent contains a compound of formula I in polymerised form. 11. A surgical cement according to claim 8 wherein the liquid component comprises a polymerisable monomer and an activator. 12. A surgical cement according to claim 1 which is radio-opaque. 13. A surgical cement according to claim 2 comprising from 0.5 to 50% w/w of a methacrylate. 14. The use of a compound of formula I, CH. I I CH 3 CCO 2 (CH 2 ) n X I in which n is an integer from 1 to 6, and X is halogen, alkoxy C1 to 6, or (trialkylsiloxy) silyl, in the manufacture of a surgical cement. 15. A method of fixing a prosthesis into a patient which comprises the application of a surgical cement according to claim 1 to an implantable prosthesis prior or during implant. 16. A method according to claim 15 wherein the implant is an orthopaedic implant.

Inventors: MILNER RICHARD, MILNER, RICHARD
Applicants: MILNER RICHARD, SMITH & NEPHEW, MILNER, RICHARD, SMITH & NEPHEW PLC
Application year: 1994
Main classification: A61L25
IPC codes: A61L24